Enhancement of ethanol reward by dopamine D3 receptor blockade

Boyce, Janel M.; Risinger, Fred O.

doi:10.1016/s0006-8993(00)02801-8

Cited by 29 publications

(19 citation statements)

References 20 publications

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“…In contrast to our findings, the mixed D 2 /D 3 receptor antagonist U99194 enhances ethanol CPP but does not affect oral alcohol self-administration in Swiss-Webster mice [31,32]. In contrast, U99194 fails to alter ethanol CPP in DBA/2J mice [86].…”

Section: Effect Of Sb-277011-a On Ethanol Self-administration and Relcontrasting

confidence: 99%

The role of central dopamine D3 receptors in drug addiction: a review of pharmacological evidence

Heidbreder

Gardner

et al. 2005

Brain Research Reviews

305

249

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The cDNA for the dopamine D 3 receptor was isolated and characterized in 1990. Subsequent studies have indicated that D 3 receptors, as well as D 3 receptor mRNA, are primarily localized in limbic regions in mammals. This finding led to the postulate that D 3 receptors may be involved in drug dependence and addiction. However, this hypothesis has been difficult to test due to the lack of compounds with high selectivity for central D 3 receptors. The interpretation of results from studies using mixed D 2 /D 3 agonists and/or antagonists is problematic because these agents have low selectivity for D 3 over D 2 receptors and it is likely that their actions are primarily related to D 2 receptor antagonism and possibly interaction with other neurotransmitter receptors. Currently, with the synthesis and characterization of new highly selective D 3 receptor antagonists such as SB-277011-A this difficulty has been surmounted. The purpose of the present article is to review, for the first time, the effects of various putative D 3 receptor selective compounds in animal models of drug dependence and addiction. The results obtained with highly selective D 3 receptor antagonists such as SB-277011-A, SB-414796, and NGB-2904 indicate that central D 3 receptors may play an important role in drug-induced reward, drug-taking, and cue-, drug-, and stressinduced reinstatement of drug-seeking behavior. Provided these results can be extrapolated to human drug addicts, they suggest that selective DA D 3 receptor antagonists may prove effective as potential pharmacotherapeutic agents to manage drug dependence and addiction.

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Section: Effect Of Sb-277011-a On Ethanol Self-administration and Relcontrasting

confidence: 99%

The role of central dopamine D3 receptors in drug addiction: a review of pharmacological evidence

Heidbreder

Gardner

et al. 2005

Brain Research Reviews

305

249

View full text Add to dashboard Cite

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“…For example, mice with a deletion of the gene for neuropeptide Y consume more ethanol than wildtype controls (Thiele et al, 1998). In addition, studies suggest that the D3 receptor negatively regulates ethanol reward and consumption; administration of the D3 agonist 7-hydroxy-2(di-n-propylamino) tetralin decreases ethanol intake and preference in rats (Cohen et al, 1998), whereas administration of the D3 antagonist U99194A enhances ethanol-induced conditioned place preference (Boyce and Risinger, 2000). Activity of one or more of these gene products may be the mechanism for the reduction of BDNF in the reinforcing-rewarding effects of ethanol.…”

Section: Rack1 Mediates the Increase In Bdnf And Decreases Behavioralmentioning

confidence: 99%

RACK1 and Brain-Derived Neurotrophic Factor: A Homeostatic Pathway That Regulates Alcohol Addiction

McGough¹,

He²,

Logrip³

et al. 2004

J. Neurosci.

226

295

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Alcoholism is a devastating disease that manifests as uncontrolled drinking. Consumption of alcohol is regulated by neurochemical systems within specific neural circuits, but endogenous systems that may counteract and thus suppress the behavioral effects of ethanol intake are unknown. Here we demonstrate that BDNF plays a role in reducing the behavioral effects of ethanol, including consumption, in rodents. We found that decreasing the levels of BDNF leads to increased behavioral responses to ethanol, whereas increases in the levels of BDNF, mediated by the scaffolding protein RACK1, attenuate these behaviors. Interestingly, we found that acute exposure of neurons to ethanol leads to increased levels of BDNF mRNA via RACK1. Importantly, acute systemic administration of ethanol and voluntary ethanol consumption lead to increased levels of BDNF expression in the dorsal striatum. Taken together, these findings suggest that RACK1 and BDNF are part of a regulatory pathway that opposes adaptations that lead to the development of alcohol addiction.

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“…For example, administration of the D 2 R/D 3 R agonist 7-hydroxy-2(di-n-propylamino)tetralin decreases ethanol self-administration and preference in rats (Cohen et al, 1998), and the D 3 R antagonist 5,6-dimethoxy-2-(di-n-propylamino)indan (U-99194A) increases ethanol-induced CPP (Boyce and Risinger, 2000). Therefore, we hypothesized that the RACK1/BDNF pathway regulates ethanol intake via the D 3 R. Here, we show that the BDNF signaling cascade is activated during voluntary ethanol consumption, leading to increased levels of D 3 R, and that BDNF-induced decreases in drinking are attenuated by D 3 R blockade.…”

Section: Introductionmentioning

confidence: 99%

The Dopamine D₃Receptor Is Part of a Homeostatic Pathway Regulating Ethanol Consumption

et al. 2006

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Enhancement of ethanol reward by dopamine D3 receptor blockade

Cited by 29 publications

References 20 publications

The role of central dopamine D3 receptors in drug addiction: a review of pharmacological evidence

The role of central dopamine D3 receptors in drug addiction: a review of pharmacological evidence

RACK1 and Brain-Derived Neurotrophic Factor: A Homeostatic Pathway That Regulates Alcohol Addiction

The Dopamine D₃Receptor Is Part of a Homeostatic Pathway Regulating Ethanol Consumption

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Enhancement of ethanol reward by dopamine D3 receptor blockade

Cited by 29 publications

References 20 publications

The role of central dopamine D3 receptors in drug addiction: a review of pharmacological evidence

The role of central dopamine D3 receptors in drug addiction: a review of pharmacological evidence

RACK1 and Brain-Derived Neurotrophic Factor: A Homeostatic Pathway That Regulates Alcohol Addiction

The Dopamine D3Receptor Is Part of a Homeostatic Pathway Regulating Ethanol Consumption

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The Dopamine D₃Receptor Is Part of a Homeostatic Pathway Regulating Ethanol Consumption